WHO recommendation on Routes of oxytocin administration ......O MMEnDATI O n O n RO UTES O f O XyT O CIn ADMInISTRATI O Recommendation WHO recommendation on routes of oxytocin administration

WHO recommendation onRoutes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth

WHO recommendation on routes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth

ISBN 978-92-4-001392-6 (electronic version) ISBN 978-92-4-001393-3 (print version)

copy World Health Organization 2020

Some rights reserved This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 30 IGO licence (CC BY-NC-SA 30 IGO httpscreativecommonsorglicensesby-nc-sa30igo)

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Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (httpwwwwipointamcenmediationrules)

Suggested citation WHO recommendation on routes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth Geneva World Health Organization 2020 Licence CC BY-NC-SA 30 IGO

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ContentsAcknowledgements v

Acronyms and abbreviations vi

Executive summary vii

Introduction vii

Target audience vii

Guideline development methods vii

Recommendation viii

1 Introduction 1

11 Background 1

12 Rationale and objectives 1

13 Target audience 2

14 Scope of the recommendation 2

15 Persons affected by the recommendation 2

2 Methods 3

21 Executive Guideline Steering Group (GSG) 3

22 WHO Steering Group 3

23 Guideline Development Group (GDG) 3

24 Evidence Synthesis Group (ESG) 4

25 External partners and observers 4

26 External Review Group (ERG) 4

27 Identification of priority questions and outcomes 4

28 Evidence identification and retrieval 5

29 Certainty assessment and grading of the evidence 5

210 Formulation of the recommendation 6

211 Management of declarations of interests 8

212 Decision-making during the GDG meeting 8

213 Document preparation 9

214 Peer review 9

3 Recommendation and supporting evidence 10

4 Dissemination adaptation and implementation of the recommendation 12

41 Recommendation dissemination 12

42 Adaptation 12

43 Implementation considerations 13

5 Research implications 13

6 Applicability issues 14

61 Anticipated impact on the organization of care and resources 14

62 Monitoring and evaluating guideline implementation 14

7 Updating the recommendation 15

8 References 16

Annex 1 External experts and who staff involved in the preparation of the recommendation 19

Annex 2 Priority outcomes used in decision-making 22

Annex 3 Summary and management of declared interests from GDG members 23

Annex 4 Evidence to Decision framework 25

Acknowledgements

The World Health Organization (WHO) Department of Sexual and Reproductive Health and Research and Department of Maternal Newborn Child and Adolescent Health and Ageing gratefully acknowledge the contributions of many individuals and organizations to the updating of this recommendation Work on this update was coordinated by Fernando Althabe Tina Lavin Olufemi Oladapo Joshua Vogel and Mariana Widmer of the Department of Sexual and Reproductive Health and Research

WHO extends its sincere thanks to Oluwarotimi Ireti Akinola Brendan Carvalho Melania Amorim Catherine Deneux-Tharaux Tippawan Liabsuetrakul Martin Meremikwu Suellen Miller Mari Nagai Hayfaa Wahabi Dilys Walker and Andrew Weeks who served as members of the Guideline Development Group (GDG) and to Ashraf Nabhan (Chair) for leading the meeting We also thank Christine East Gill Gyte Justus Hofmeyr Syeda Batool Mazhar Enrique Oyarzun and Qian Xu who were members of the External Review Group (ERG) WHO also gratefully acknowledges the contribution of the members of the Executive Guideline Steering Group (GSG)

Edgardo Abalos Anna Cuthbert Virginia Diaz Kenneth Finlayson Leanne Jones Frances Kellie and Myfanwy Williams reviewed the scientific evidence prepared the Grading of Recommendations Assessment Development and Evaluation (GRADE) tables and drafted the narrative summary of the evidence Fernando Althabe Olufemi Oladapo Mariana Widmer and Joshua Vogel revised the narrative summaries and double-checked the corresponding GRADE tables and prepared the Evidence to Decision (EtD) frameworks The ERG peer reviewed the final document prior to executive clearance by WHO and publication

We acknowledge the various organizations that were represented by observers including Deborah Armbruster (United States Agency for International Development [USAID]) Ingela Wiklund (International Confederation of Midwives [ICM]) and Carlos Fuchtner (International Federation of Gynecology and Obstetrics [FIGO]) We also appreciate the contributions of staff at the WHO regional offices including Nino Berdzuli Bremen De Mucio Hayfa Elamin Chandani Anoma Jayathilaka Ramez Khairi Mahaini Howard Sobel and Claudio Sosa

WHO acknowledges the financial support for this work received from USAID and the UNDPndashUNFPAndashUNICEFndashWHOndashWorld Bank Special Programme of Research Development and Research Training in Human Reproduction the Department of Sexual and Reproductive Health and Research WHO emphasizes that donors do not participate in any decision related to the guideline development process including the composition of research questions membership of the guideline development groups conducting and interpretation of systematic reviews or formulation of the recommendations The views of the funding bodies have not influenced the content of this recommendation

Acronyms and abbreviations

CerQUAL Confidence in the Evidence from Reviews of Qualitative Research

DOI declaration of interest

ERG Evidence Review Group

ESG Evidence Synthesis Group

EtD Evidence to Decision

FIGO International Federation of Gynecology and Obstetrics

GDG Guideline Development Group

GRADE Grading of Recommendations Assessment Development and Evaluation

GSG Guideline Steering Group

HRP UNDPndashUNFPAndashUNICEFndashWHOndashWorld Bank Special Programme of Research Development and Research Training in Human Reproduction

ICM International Confederation of Midwives

IM intramuscular

IU international units

IV intravenous

MPH-GDG WHO Maternal and Perinatal Health Guideline Development Group

PICO population (P) intervention (I) comparator (C) outcome (O)

PPH postpartum haemorrhage

UNDP United Nations Development Programme

UNFPA United Nations Population Fund

UNICEF United Nations Childrenrsquos Fund

USAID United States Agency for International Development

WHO World Health Organization

Executive summary

IntroductionPostpartum haemorrhage (PPH) is commonly defined as a blood loss of 500 mL or more within 24 hours after birth and affects about 5 of all women giving birth around the world Globally nearly one quarter of all maternal deaths are associated with PPH and in most low-income countries it is the main cause of maternal mortality Improving care during childbirth to prevent PPH is a necessary step towards the achievement of the health targets of the third Sustainable Development Goal (SDG 3) particularly target 31 reduce the global maternal mortality ratio to less than 70 per 100 000 live births by 2030 Efforts to prevent and reduce morbidity and mortality due to PPH can help to address the profound inequities in maternal and perinatal health globally To achieve this skilled health personnel health managers policy-makers and other stakeholders need up-to-date and evidence-informed recommendations to guide clinical policies and practices

In 2019 the Executive Guideline Steering Group (GSG) for World Health Organization (WHO) maternal and perinatal health recommendations prioritized the updating of the existing WHO recommendations for intravenous (IV) versus intramuscular (IM) oxytocin for prevention of PPH after vaginal birth in response to the availability of new evidence The recommendation in this document thus supersedes the previous WHO recommendations for the prevention of PPH as published in the 2012 guideline WHO recommendations for the prevention and treatment of postpartum haemorrhage

Target audienceThe primary audience for these recommendations includes health professionals who are responsible for developing national and local health-care guidelines and protocols (particularly those related to PPH prevention and treatment) and those involved in the provision of care to women and their newborns during labour and childbirth including midwives nurses general medical practitioners and obstetricians as well as managers of maternal and child health programmes and relevant staff in ministries of health and training institutions in all settings

Guideline development methodsThe updating of these recommendations was guided by standardized operating procedures in accordance with the process described in the WHO handbook for guideline development The recommendations were initially developed and updated using this process namely (i) identification of priority questions and outcomes (ii) retrieval of evidence (iii) assessment and synthesis of evidence (iv) formulation of the recommendations and (v) planning for the dissemination implementation impact evaluation and future updating of the recommendations

The scientific evidence supporting the recommendation was synthesized using the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach An updated systematic review was used to prepare the evidence profiles for the prioritized question WHO convened a meeting on 11ndash12 March 2020 where the Guideline Development Group (GDG) members reviewed deliberated and achieved consensus on the strength and direction of the recommendation presented herein Through a structured process the GDG reviewed the balance between the desirable and undesirable effects and the overall certainty of supporting evidence values and preferences of stakeholders resource requirements and cost-effectiveness acceptability feasibility and equity

RecommendationThe GDG reviewed the balance between the desirable and undesirable effects and the overall certainty of supporting evidence values and preferences of stakeholders resource requirements and cost-effectiveness acceptability feasibility and equity The GDG issued the new recommendation on IV versus IM oxytocin for prevention of PPH after vaginal birth with remarks and implementation considerations To ensure that the recommendation is correctly understood and applied in practice guideline users may want to refer to the remarks as well as to the evidence summary including the considerations on implementation

The use of oxytocin (10 international units [IU] intramuscular intravenous) is recommended for the prevention of postpartum haemorrhage for all births In situations where women giving birth vaginally already have intravenous access the slow intravenous administration of 10 IU oxytocin is recommended in preference to intramuscular administration

(Context-specific recommendation)

Justification There is clear evidence in favour of intravenous oxytocin in terms of health

outcomes When compared to intramuscular oxytocin intravenous oxytocin reduces the risk of postpartum haemorrhage severe postpartum haemorrhage blood transfusion and severe maternal morbidity with no clear differences in undesirable effects While it is uncertain whether intravenous administration is more cost-effective routine intravenous oxytocin use for postpartum haemorrhage prevention imposes additional resource requirements may negatively impact womenrsquos comfort and can increase health inequities The feasibility of intravenous administration may also vary in different settings However in situations where intravenous access is already in place at vaginal birth the clinical benefits of intravenous administration outweigh these other considerations

Remarks The Guideline Development Group acknowledged that either intravenous or

intramuscular oxytocin is effective in preventing postpartum haemorrhage and both routes of administration are currently recommended by WHO for this indication

While noting that the balance of effects favours intravenous oxytocin for important health outcomes the Guideline Development Group placed its emphasis on other considerations (including feasibility and impacts on resources health equity and womenrsquos comfort) as well as studies suggestive of possible safety concerns with a rapid intravenous bolus of oxytocin In instances where women already have intravenous access (for another medical indication) it is recommended to administer oxytocin intravenously

The Guideline Development Group acknowledged existing WHO recommendations against the routine use of intravenous fluids during labour and childbirth with emphasis on the widespread and unnecessary use of routine administration of intravenous fluids for all women in labour in many health facilities in low-middle and high-income settings that increases cost and impacts on resource use The Guideline Development Group emphasized that intravenous access should not be placed routinely for the sole purpose of administering intravenous oxytocin for postpartum haemorrhage prevention

The Guideline Development Group noted that the previous trials considered for this question have all administered an oxytocin dose of 10 IU intravenously for postpartum haemorrhage prevention during vaginal birth However the speed of injection ranged from 1 minute (for bolus injection) to 40 minutes (for infusion) and volume of dilution from 1 mL (for bolus injection) to 1000 mL of saline (for infusion) There is no direct evidence comparing the different regimens for administering intravenous oxytocin during vaginal birth and there were no safety concerns (such as hypotension or tachycardia) in trials comparing slow intravenous administration of 10 IU oxytocin over 1 minute with 10 IU intramuscular oxytocin However observational studies in women undergoing caesarean section suggest that rapid intravenous injection results in harmful haemodynamic effects Therefore the Guideline Development Group suggests avoiding a rapid injection and agreed that the 10 IU oxytocin dose should preferably be diluted and administered slowly

This recommendation reflects available evidence from direct comparison of intravenous versus intramuscular oxytocin during vaginal birth For women undergoing caesarean section WHO currently recommends 10 IU for postpartum haemorrhage prevention without preference for intravenous or intramuscular

This recommendation does not relate to the use of oxytocin for other obstetric indications (such as labour induction labour augmentation or treatment of postpartum haemorrhage)

1 Introduction

11 Background An estimated 295 000 women and adolescent girls died as a result of pregnancy and childbirth-related complications in 2017 and around 99 of these deaths occurred in low-resource settings (1) Obstetric haemorrhage especially postpartum haemorrhage (PPH) is responsible for more than a quarter of all maternal deaths worldwide (2) In most low-income countries PPH is the leading cause of maternal deaths Thus improving access to safe and effective interventions to prevent PPH is critical to World Health Organization (WHO) strategic priorities (particularly universal health coverage) for achieving the targets of the third Sustainable Development Goal (SDG 3) (3)

International human rights law includes fundamental commitments of States to enable women and adolescent girls to survive pregnancy and childbirth as part of their enjoyment of sexual and reproductive health and rights and living a life of dignity (4) WHO envisions a world where ldquoevery pregnant woman and newborn receives quality care throughout pregnancy childbirth and the postnatal periodrdquo (5) To provide good-quality care skilled health personnel at all levels of the health system need to have access to appropriate medications and training in relevant procedures (6) Health-care providers health managers health policy-makers and other stakeholders also need up-to-date evidence-informed recommendations to guide clinical policies and practices to optimize quality of care and improve health-care outcomes

PPH is commonly defined as a blood loss of 500 mL or more within 24 hours after birth and affects about 5 of all women giving birth around the world (78) Severe maternal complications such as organ dysfunction or death generally occur following substantial blood loss that compromises maternal haemodynamic stability Uterine atony is the most common cause of PPH and a leading cause of PPH-related maternal mortality worldwide (9) Genital tract trauma (including vaginal or cervical lacerations and uterine rupture) retained placental tissue or maternal bleeding disorders can cause PPH Although PPH can occur in any woman even those without risk factors grand multiparity prolonged labour prior history of PPH and multiple gestation are associated with an increased risk of bleeding after birth (10) In addition anaemia is a common aggravating factor (11) The majority of PPH-associated complications could be avoided by the use of prophylactic uterotonics during the third stage of labour (that is the time between the delivery of the baby and complete expulsion of the placenta)

Oxytocin is one such uterotonic and is listed on the WHO model list of essential medicines for this indication (12) It is a synthetic cyclic peptide form of the naturally occurring posterior pituitary hormone (1314) Oxytocin binds to the oxytocin receptor in the uterine myometrium stimulating contraction of the uterine smooth muscle Oxytocin can be administered intravenously where its action is almost immediate with a peak in concentration after 30 minutes (1314) It can also be administered intramuscularly with a slower onset of action taking 3ndash7 minutes with a longer-lasting clinical effect of up to one hour (1314) Oxytocin requires protection from light and must be stored at 2ndash8 degC (15)

12 Rationale and objectivesWHO has established a new process for prioritizing and updating maternal and perinatal health recommendations whereby an international group of independent experts ndash the Executive Guideline Steering Group (GSG) ndash oversees a systematic prioritization of maternal and perinatal health recommendations in most urgent need of updating (1617) Recommendations are prioritized for updating on the basis of changes or important new uncertainties in the underlying evidence base on benefits harms values placed on outcomes acceptability feasibility equity resource use cost-effectiveness or factors affecting implementation The Executive GSG prioritized updating of the WHO recommendations for intravenous (IV) versus intramuscular (IM) oxytocin for prevention 1

of PPH after vaginal birth in anticipation of the publication of new and potentially important evidence on these interventions

These updated recommendations were developed in accordance with the standards and procedures in the WHO handbook for guideline development including synthesis of available research evidence use of the Grading of Recommendations Assessment Development and Evaluation (GRADE)1 and GRADE Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CerQUAL)2 methodologies and formulation of recommendations by a Guideline Development Group (GDG) composed of international experts and stakeholders (18) The recommendation published in this document thus supersedes the previous recommendations for IV versus IM oxytocin for prevention of PPH after vaginal birth that were published in 2012 in WHO recommendations for the prevention and treatment of postpartum haemorrhage (19) The primary aim of these recommendations is to improve the quality of care and outcomes for women giving birth as they relate to PPH and its complications This recommendation thus provides guidance for use of IV versus IM oxytocin for prevention of PPH after vaginal birth

13 Target audienceThe primary audience includes health professionals who are responsible for developing national and local health-care guidelines and protocols (particularly those related to PPH prevention and treatment) and those involved in the provision of care to women during labour and childbirth including midwives nurses general medical practitioners and obstetricians as well as managers of maternal and child health programmes and relevant staff in ministries of health and training institutions in all settings

This recommendation will also be of interest to women giving birth in a range of resource settings (low to high) as well as members of professional societies involved in the care of pregnant women staff of nongovernmental organizations concerned with promoting people-centred maternal care and implementers of programmes

14 Scope of the recommendationFramed using the Population (P) Intervention (I) Comparison (C) Outcome (O) (PICO) format the question for this recommendation was

For women in the third stage of labour (P) does administration of IV oxytocin for PPH prevention (I) compared with IM oxytocin (C) improve maternal and infant outcomes (O)

15 Persons affected by the recommendationThe population affected by this recommendation includes all pregnant women in low- middle- or high-income settings

1 Further information is available at httpwwwgradeworkinggrouporg 2 Further information is available at httpswwwcerqualorg

2 Methods

The recommendation was developed using standardized operating procedures in accordance with the process described in the WHO handbook for guideline development (18) In summary the process included (i) identification of the priority question and critical outcomes (ii) retrieval of evidence (iii) assessment and synthesis of evidence (iv) formulation of the recommendation and (v) planning for the dissemination implementation impact evaluation and updating of the recommendation

In 2019 IV versus IM oxytocin for prevention of PPH after vaginal birth was identified by the Executive GSG as a high priority for development of a recommendation in response to new potentially important evidence on this question Six main groups were involved in this process with their specific roles described in the following sections

21 Executive Guideline Steering Group (GSG)The Executive GSG is an independent panel of 14 external experts and relevant stakeholders from the six WHO regions African Region Region of the Americas Eastern Mediterranean Region European Region South-East Asia Region and Western Pacific Region The Executive GSG advises WHO on the prioritization of new and existing PICO questions in maternal and perinatal health for development or updating of recommendations (1617)

22 WHO Steering GroupThe WHO Steering Group comprising WHO staff members from the Department of Sexual and Reproductive Health and Research and the Department of Maternal Newborn Child and Adolescent Health and Ageing managed the process of updating the recommendations The WHO Steering Group drafted the key recommendation questions in PICO format engaged the systematic review teams and guideline methodologists (that is the Evidence Synthesis Group [ESG]) as well as the members of the GDG and the External Review Group (ERG) (see below) In addition the WHO Steering Group supervised the retrieval and syntheses of evidence organized the GDG meetings drafted and finalized the guideline document and will also manage the guideline dissemination implementation and impact assessment The members of the WHO Steering Group are listed in Annex 1

23 Guideline Development Group (GDG)The WHO Steering Group identified a pool of approximately 50 experts and relevant stakeholders from the six WHO regions to constitute the WHO Maternal and Perinatal Health Guideline Development Group (MPH-GDG) This pool consists of a diverse group of experts who are skilled in the critical appraisal of research evidence implementation of evidence-informed recommendations guideline development methods and clinical practice policy and programmes relating to maternal and perinatal health Members of the MPH-GDG are identified in a way that ensures geographic representation and gender balance and there were no perceived or real conflicts of interest Membersrsquo expertise cuts across thematic areas within maternal and perinatal health

From the MPH-GDG pool 14 external experts and relevant stakeholders were invited to participate as members of the GDG for updating this recommendation Those selected were a diverse group with expertise in research guideline development methods gender equity and rights clinical policy and programmes relating to PPH prevention and treatment

The 14 GDG members for this recommendation were also selected in a way that ensured geographic representation and gender balance and there were no important conflicts of interest The GDG appraised the evidence that was used to inform the recommendation advised on the interpretation of this evidence formulated the final recommendation based on the draft prepared by the WHO Steering Group and reviewed and reached unanimous consensus for the recommendation in the final document The members of the GDG are listed in Annex 1 2

24 Evidence Synthesis Group (ESG)WHO convened an ESG composed of guideline methodologists and systematic review teams to conduct or update systematic reviews appraise the evidence and develop the Evidence to Decision (EtD) frameworks A systematic review on this question was updated supported by the Cochrane Pregnancy and Childbirth Group The WHO Steering Group reviewed and provided input into the updated protocol and worked closely with the Cochrane Pregnancy and Childbirth Group to appraise the evidence using the GRADE methodology Representatives of the Cochrane Pregnancy and Childbirth Group and a methodologist attended the GDG meeting to provide an overview of the available evidence and GRADE tables and to respond to technical queries from the GDG

Evidence for the other domains of the GRADE EtD frameworks were obtained from two existing systematic qualitative reviews exploring what matters to women during childbirth and what matters to women and health-care providers in relation to interventions for the prevention of PPH (2021) A systematic review on the cost-effectiveness of IV versus IM oxytocin (updated to March 2020) was used for evidence in the cost-effectiveness domain in the EtD framework (22) All members of the ESG attended the GDG meetings to provide an overview of the synthesized evidence and to respond to technical queries from the GDG The members of the ESG are listed in Annex 1

25 External partners and observersRepresentatives of the United States Agency for International Development (USAID) the International Confederation of Midwives (ICM) and the International Federation of Gynecology and Obstetrics (FIGO) participated in the GDG meeting as observers These organizations with their long history of collaboration with WHO in maternal and perinatal guideline dissemination and implementation were identified as potential implementers of the recommendations The list of observers who participated in the GDG meeting is included in Annex 1

26 External Review Group (ERG)The ERG included six technical experts with interests and expertise in the provision of evidence-based care to prevent and treat PPH The group was geographically diverse and gender balanced and the members had no important conflicts of interest The experts reviewed the final document to identify any factual errors and commented on the clarity of language contextual issues and implications for implementation They ensured that the decision-making processes had considered and incorporated contextual values and the preferences of persons affected by the recommendations health-care professionals and policy-makers It was not within the remit of this group to change the recommendations that were formulated by the GDG Members of the ERG are listed in Annex 1

27 Identification of priority questions and outcomesThe priority outcomes were aligned with those from the 2012 WHO recommendations for prevention and treatment of postpartum haemorrhage (19) These outcomes were initially identified through a search of scientific databases for relevant published systematic reviews and a prioritization of outcomes by the GDG for the 2012 guideline After due consideration of the recently published core outcome set for prevention and treatment of PPH (23) two additional outcomes ndash maternal well-being and maternal satisfaction ndash were included for this update to ensure that evidence synthesis and recommendation decision-making by the GDG were driven by outcomes that are important to women and to ensure that the final set of recommendations would be woman-centred All the outcomes were included in the scope of this document for evidence searching retrieval synthesis grading and formulation of the recommendation The list of priority outcomes is provided in Annex 2

28 Evidence identification and retrieval Evidence to support this update was derived from several sources by the ESG working in collaboration with the WHO Steering Group

281 Evidence on the effects of IV versus IM oxytocin for PPH prevention after vaginal birth

An existing systematic review was updated for the purpose of this update (24) This systematic review was the primary source of evidence for this recommendation

Randomized controlled trials relevant to the key question were screened by the review authors and data on relevant outcomes and comparisons were entered into the Review Manager 5 (RevMan) software The RevMan file was retrieved from the Cochrane Pregnancy and Childbirth Group and customized to reflect the key comparisons and outcomes (those that were not relevant to the recommendation were excluded) The RevMan file was then exported to GRADE profiler software (GRADEpro) and GRADE criteria were used to critically appraise the retrieved scientific evidence (25) Finally evidence profiles (in the form of GRADE summary of findings tables) were prepared for comparisons of interest including the assessment and judgements for each outcome and the estimated risks

282 Evidence on values resource use and cost-effectiveness equity acceptability and feasibility

Evidence from two systematic reviews were used to inform the acceptability feasibility and equity domains as they relate to the EtD framework for IV versus IM oxytocin administration for the prevention of PPH (2021) A review of qualitative studies evaluating ldquowhat women wantrdquo from intrapartum care was used for the acceptability and equity domains relating to medical interventions feelings about labour and birth recognition of complications and receiving information on introduced interventions (20) Another qualitative review explored the perceptions on PPH prevention and treatment of health-care providers and women including the benefits of oxytocin use to prevent PPH and the factors influencing effective use of oxytocin (21) A systematic review of the literature found no direct evidence on the relative cost-effectiveness of IV oxytocin compared with IM oxytocin to prevent PPH (22)

29 Certainty assessment and grading of the evidenceThe certainty assessment of the body of evidence for each outcome was performed using the GRADE approach (26) Using this approach the certainty of evidence for each outcome was rated as rdquohighrdquo rdquomoderaterdquo rdquolowrdquo or rdquovery lowrdquo based on a set of established criteria The final rating of certainty of evidence was dependent on the factors briefly described below

Study design limitations The risk of bias was first examined at the level of each individual study and then across the studies contributing to the outcome For randomized trials certainty was first rated as ldquohighrdquo and then downgraded by one (ldquomoderaterdquo) or two (ldquolowrdquo) levels depending on the minimum criteria met by the majority of the studies contributing to the outcome

Inconsistency of the results The similarity in the results for a given outcome was assessed by exploring the magnitude of differences in the direction and size of effects observed in different studies The certainty of evidence was not downgraded when the direction of the findings were similar and confidence limits overlapped whereas it was downgraded when the results were in different directions and confidence limits showed minimal or no overlap

Indirectness The certainty of evidence was downgraded when there were serious or very serious concerns regarding the directness of the evidence ndash that is whether there were important differences between the research reported and the context for which the recommendation was being prepared Such differences were related for instance to populations interventions comparisons or outcomes of interest

Imprecision This assessed the degree of uncertainty around the estimate of effect As this is often a function of sample size and number of events studies with relatively few participants or events and thus wide confidence intervals around effect estimates were downgraded for imprecision

Publication bias The certainty rating could also be affected by perceived or statistical evidence of bias to underestimate or overestimate the effect of an intervention as a result of selective publication based on study results Downgrading evidence by one level was considered where there was strong suspicion of publication bias

Certainty of evidence assessments are defined according to the GRADE approach

High certainty We are very confident that the true effect lies close to that of the estimate of the effect

Moderate certainty We are moderately confident in the effect estimate The true effect is likely to be close to the estimate of the effect but there is a possibility that it is substantially different

Low certainty Our confidence in the effect estimate is limited The true effect may be substantially different from the estimate of the effect

Very low certainty We have very little confidence in the effect estimate The true effect is likely to be substantially different from the estimate of effect

The findings of the qualitative reviews were appraised for quality using the GRADE-CERQual tool (27) The GRADE-CERQual tool which uses a similar conceptual approach to other GRADE tools provides a transparent method for assessing and assigning the level of confidence that can be placed in evidence from reviews of qualitative research The systematic review team used the GRADE-CERQual tool to assign a level of confidence (high moderate low and very low) to each review finding according to four components methodological limitations of the individual studies adequacy of data coherence and relevance to the review question of the individual studies contributing to a review finding Findings from individual cost-effectiveness studies were reported narratively for each comparison of interest

210 Formulation of the recommendationThe WHO Steering Group supervised and finalized the preparation of summary of findings tables and narrative evidence summaries in collaboration with the ESG using the GRADE EtD framework EtD frameworks include explicit and systematic consideration of evidence on prioritized interventions in terms of specified domains effects values resources equity acceptability and feasibility For the priority questions judgements were made on the impact of the intervention on each domain to inform and guide the decision-making process Using the EtD framework template the WHO Steering Group and ESG created summary documents for each priority question covering evidence on each domain

Effects The evidence on the priority outcomes was summarized in this domain to answer the questions ldquoWhat are the desirable and undesirable effects of the interventionrdquo and ldquoWhat is the certainty of the evidence on effectsrdquo Where benefits clearly outweighed harms for outcomes that are highly valued by women or vice versa there was a greater likelihood of a clear judgement in favour of or against the intervention respectively Uncertainty about the net benefits or harms or small net benefits usually led to a judgement that did not favour the intervention or the comparator The higher the certainty of the evidence of benefits across outcomes the higher the likelihood of a judgement in favour of the intervention In the absence of evidence of benefits evidence of potential harm led to a recommendation against the intervention Where the intervention showed evidence of potential harm and was also found to have evidence of important benefits depending on the level of certainty and the likely impact of the harm such evidence of potential harm was more likely to result in a context-specific recommendation with the context explicitly stated within the recommendation

Values This domain relates to the relative importance assigned to the outcomes associated with the intervention by those affected how such importance varies within and across settings and whether this importance is surrounded by any uncertainty The question asked was ldquoIs there important uncertainty or variability in how much women value the main outcomes associated with the interventionrdquo When the intervention resulted in benefit for outcomes that most women consistently value (regardless of setting) this was more likely to lead to a judgement in favour of the intervention This domain together with the ldquoeffectsrdquo domain (see above) informed the ldquobalance of effectsrdquo judgement

Resources For this domain the questions asked were ldquoWhat are the resources associated with the interventionrdquo and ldquoIs the intervention cost-effectiverdquo The resources required to implement IV oxytocin mainly include the costs of providing supplies and training A judgement in favour of or against the intervention was likely where the resource implications were clearly advantageous or disadvantageous respectively

Acceptability For this domain the question was ldquoIs the intervention acceptable to women and health-care providersrdquo Qualitative evidence from systematic reviews on the views and experiences of women and providers with the prevention and treatment of PPH informed the judgements for this domain (2021) The lower the acceptability the lower the likelihood of a judgement in favour of the intervention

Feasibility The feasibility of implementing this intervention depends on factors such as the resources infrastructure and training requirements and the perceptions of health-care providers responsible for administering it The question addressed was ldquoIs it feasible for the relevant stakeholders to implement the interventionrdquo Qualitative evidence from the systematic reviews on womenrsquos and providersrsquo views and experiences with treatment of PPH was used to inform judgements for this domain (2021) Where major barriers were identified it was less likely that a judgement would be made in favour of the intervention

Equity This domain encompasses evidence or considerations as to whether or not the intervention would reduce health inequities Therefore this domain addressed the question ldquoWhat is the anticipated impact of the intervention on equityrdquo The findings of qualitative reviews of evidence and two rapid reviews as well as the experiences and experiences of the GDG members were used to inform judgements for this domain (2021) The intervention was likely to be recommended if its proven (or anticipated) effects reduce (or could reduce) health inequalities among different groups of women and their families

For each of the above domains additional evidence of potential harms or unintended consequences are described in the Additional considerations subsections Such considerations were derived from studies that might not have directly addressed the priority question but provided pertinent information in the absence of direct evidence These considerations were extracted from single studies systematic reviews or other relevant sources

The WHO Steering Group provided the EtD frameworks including evidence summaries summary of findings tables and other documents related to each recommendation to the GDG members two weeks in advance of the GDG meeting The GDG members were asked to review and provide comments (electronically) on the documents before the GDG meeting During the GDG meeting (11ndash12 March 2020) which was conducted under the leadership of the GDG chairperson the GDG members collectively reviewed the EtD frameworks and any comments received through preliminary feedback and formulated the recommendations The purpose of the meeting was to reach consensus on each recommendation including its direction and in some instances the specific context based on explicit consideration of the range of evidence presented in each EtD framework and the judgement of the GDG members The GDG was asked to select one of the following categories for the recommendation

Recommended This category indicates that the intervention should be implemented

Not recommended This category indicates that the intervention should not be implemented

Recommended only in specific contexts (context-specific recommendation) This category indicates that the intervention is applicable only to the condition setting or population specified in the recommendation and should only be implemented in these contexts

Recommended only in the context of rigorous research (research-context recommendation) This category indicates that there are important uncertainties about the intervention With this category of recommendation implementation can still be undertaken on a large scale provided it takes the form of research that addresses unanswered questions and uncertainties related both to effectiveness of the intervention or option and its acceptability and feasibility

211 Management of declarations of interestsWHO has a robust process to protect the integrity of its normative work as well as to protect the integrity of individual experts with whom it collaborates WHO requires that experts serving in an advisory role disclose any circumstances that could give rise to actual or ostensible conflicts of interest The disclosure and the appropriate management of relevant financial and non-financial conflicts of interest of GDG members and other external experts and contributors are a critical part of guideline development at WHO According to WHO regulations all experts must declare their interests prior to participation in WHO guideline development processes and meetings according to the guidelines for declaration of interest (DOI) for WHO experts (18) All GDG members were therefore required to complete a standard WHO DOI form before engaging in the guideline development process and before participating in the guideline-related processes The WHO Steering Group reviewed all declarations before finalizing the expertsrsquo invitations to participate Where any conflict of interest was declared the WHO Steering Group determined whether such conflicts were serious enough to affect an expertrsquos objective judgement in the guideline and recommendation development process To ensure consistency the WHO Steering Group applied the criteria for assessing the severity of conflicts of interests as outlined in the WHO handbook for guideline development to all participating experts All findings from the DOI statements received were managed in accordance with the WHO procedures to assure the work of WHO and the contributions of its experts is actually and ostensibly objective and independent The names and biographies of individuals were published online four weeks prior to the meeting Where a conflict of interest was not considered significant enough to pose any risk to the guideline development process or to reduce its credibility the experts were only required to openly declare such conflicts of interest at the beginning of the GDG meeting and no further actions were taken Annex 3 shows a summary of the DOI statements and how conflicts of interest declared by invited experts were managed by the WHO Steering Group

212 Decision-making during the GDG meetingDuring the meeting the GDG reviewed and discussed the evidence summary and sought clarification In addition to evaluating the balance between the desirable and undesirable effects of the intervention and the overall certainty of the evidence the GDG applied additional criteria based on the GRADE EtD framework to determine the recommendation These criteria included stakeholdersrsquo values resource implications acceptability feasibility and equity Considerations were based on the experiences and opinions of the GDG members and supported by evidence from a literature search where available EtD tables were used to describe and synthesize these considerations

Decisions were made based on consensus defined as the agreement by three quarters or more of the participants None of the GDG members expressed opposition to the recommendation

213 Document preparationPrior to the online meeting the WHO Steering Group prepared a draft version of the GRADE evidence profiles the evidence summary and other documents relevant to the GDGrsquos deliberation The draft documents were made available to the participants of the meeting two weeks before the meeting for their comments During the meeting these documents were modified in line with the participantsrsquo deliberations and remarks Following the meeting members of the WHO Steering Group drafted a full guideline document to accurately reflect the deliberations and decisions of the participants The draft document was sent electronically to the GDG and the ERG for their final review and approval

214 Peer reviewFollowing review and approval by GDG members the final document was sent to eight external independent experts (comprising the ERG) who were not involved in the guideline panel for peer review The WHO Steering Group evaluated the inputs of the peer reviewers for inclusion in this document After the meeting and external peer review the modifications made by the WHO Steering Group to the document consisted only of the correction of factual errors and improving language to address any lack of clarity

3 Recommendation and supporting evidence

The following section outlines the recommendation and the corresponding narrative summary of evidence for the prioritized question The EtD table summarizing the balance between the desirable and undesirable effects and the overall certainty of the supporting evidence values and preferences of stakeholders resource requirements cost-effectiveness acceptability feasibility and equity that were considered in determining the recommendation is presented in the EtD framework (Annex 4)

The following recommendation was adopted by the GDG Evidence on the effectiveness of this intervention was derived from the updated systematic review and summarized in GRADE tables (Annex 4) The certainty of the supporting evidence was rated as ldquomoderaterdquo for most of the critical outcomes

To ensure that the recommendation is correctly understood and appropriately implemented in practice additional remarks reflecting the summary of the discussion by the GDG are included under the recommendation

The use of oxytocin (10 international units [IU] intramuscularintravenous) is recommended for the prevention of postpartum haemorrhage for all births In situations where women giving birth vaginally already have intravenous access the slow intravenous administration of 10 IU oxytocin is recommended in preference to intramuscular administration

intramuscular oxytocin is effective in preventing postpartum haemorrhage and both routes of administration are currently recommended by WHO for this indication (19)

The Guideline Development Group acknowledged existing WHO recommendations against the routine use of intravenous fluids during labour and childbirth with emphasis on the widespread and unnecessary use of routine administration of intravenous fluids for all women in labour in many health facilities in low- middle- and high-income settings that increases cost and impacts on resource use (28) The Guideline Development Group emphasized that intravenous access should not be placed routinely for the sole purpose of administering intravenous oxytocin for postpartum haemorrhage prevention

The Guideline Development Group noted that the previous trials considered for this question have all administered an oxytocin dose of 10 IU intravenously for postpartum haemorrhage prevention during vaginal birth However the speed of injection ranged from 1 minute (for bolus injection) to 40 minutes (for infusion) and volume of dilution from 1 mL (for bolus injection) to 1000 mL of saline (for infusion) There is no direct evidence comparing the different regimens for administering intravenous oxytocin during vaginal birth and there were no safety concerns (such as hypotension or tachycardia) in trials comparing slow intravenous administration of 10 IU oxytocin over 1 minute with 10 IU intramuscular oxytocin (2930) However observational studies in women undergoing caesarean section suggest that rapid intravenous results in harmful haemodynamic effects (3031) Therefore the Guideline Development Group suggests avoiding a rapid injection and agreed that the 10 IU oxytocin dose should preferably be diluted and administered slowly

This recommendation reflects available evidence from direct comparison of intravenous versus intramuscular oxytocin during vaginal birth For women undergoing caesarean section WHO currently recommends 10 IU for postpartum haemorrhage prevention without preference for intravenous or intramuscular (19)

4 Dissemination adaptation and implementation of the recommendation

The dissemination and implementation of this recommendation are to be considered by all stakeholders involved in the provision of care for pregnant women at the international national and local levels There is a vital need to increase womenrsquos access to maternal health care and to strengthen the capacity at health-care facilities of all levels to ensure they can provide high-quality services to all women giving birth It is therefore crucial that this recommendation be translated into care packages and programmes at country and health-care facility levels where appropriate

41 Recommendation dissemination The recommendation will be disseminated through WHO regional and country offices ministries of health professional organizations WHO collaborating centres other United Nations agencies and nongovernmental organizations among others This recommendation will also be available on the WHO website and the WHO Reproductive Health Library1 Updated recommendations are also routinely disseminated during meetings or scientific conferences attended by WHO maternal and perinatal health staff

The recommendation document will be translated into the six United Nations languages and disseminated through the WHO regional offices Technical assistance will be provided to any WHO regional office willing to translate the full recommendation into any of these languages

42 Adaptation National and subnational subgroups may be established to adapt and implement this recommendation based on an existing strategy This process may include the development or revision of existing national guidelines or protocols based on the updated recommendation

Existing global models such as those for WHO antenatal and intrapartum care guidelines can be adapted to different countries contexts and individual needs and preferences of women The conceptual basis of these models is to drive improvements in the quality of maternal health care by aiming to achieve the best possible physical emotional and psychological outcomes for the woman and her baby irrespective of the influence of generic policies that may exist within and across health systems and countries Both models address relevant health policy organizational and user-level considerations These models thus support implementation of WHO recommendations and are intended to be adapted by stakeholders and partners at regional country and local levels into locally appropriate documents and tools

The successful introduction of evidence-based policies (relating to updated recommendations) depends on well-planned and participatory consensus-driven processes of adaptation and implementation These processes may include the development or revision of existing national or local guidelines and protocols often supported by ministries of health United Nations agencies local professional societies and other relevant leadership groups An enabling environment should be created for the use of this recommendation including changes in the behaviour of health-care practitioners to enable the use of evidence-based practices

In the context of humanitarian emergencies adaptation of the current recommendation should consider the integration and alignment with other response strategies Additional considerations to the unique needs of women in emergency settings including their values and preferences should be made Context-specific tools and toolkits may be required

1 Available at wwwwhointrhl

in addition to standard tools to support the implementation of the recommendation in humanitarian emergencies by stakeholders

43 Implementation considerations Oxytocin should only be given by skilled health personnel who have been trained to safely

administer injectable uterotonics

Oxytocin is relatively inexpensive and widely available however it requires cold chain refrigerated transport and storage (2ndash8 degC) In settings where this cannot be guaranteed the quality efficacy and effectiveness of oxytocin may be adversely affected

It is advised that programmes to implement uterotonics for PPH prevention ensure women are adequately informed in advance about the need to use a uterotonic to prevent PPH the available uterotonic options the possible side effects of these options and their rights to choose what care they receive

An enabling environment should be created for the implementation of this recommendation including education to support behaviour change among skilled health personnel to facilitate the use of evidence-based practices

National health systems need to ensure that supplies of good-quality uterotonics and the necessary equipment are available wherever maternity services are provided This includes establishing robust and sustainable regulatory procurement and effective cold chain and logistics processes that can ensure good-quality medicines and equipment are obtained transported and stored correctly

Procurement agencies at all levels of supply chains should procure only quality-assured uterotonic medicines that are labelled for storage at 2ndash8 degC in single-use ampoules or vials of oxytocin of 10 IU per mL (10 IUmL) While some manufacturer labelling may seem to indicate that oxytocin is stable at room temperature stability may not have been tested in the much warmer conditions that may be prevalent in some countries and different formulations have different stability characteristics To prevent its degradation and to safeguard its quality oxytocin should always be stored in refrigeration regardless of labelling

5 Research implications

The GDG identified important knowledge gaps that need to be addressed through primary research which may have an impact on this recommendation The following question was identified as one that demands urgent priority

What is the optimal effective regimen of IV oxytocin for PPH prevention after vaginal birth

6 Applicability issues

61 Anticipated impact on the organization of care and resources Implementing this evidence-based recommendation requires resources for sustainable procurement and storage of uterotonic drugs The GDG noted that updating training curricula and providing training on the recommendation would increase its impact and facilitate its implementation Standardization of care by including this recommendation into existing intrapartum and immediate postpartum care packages can encourage behaviour change in health-care providers

As part of efforts to implement this recommendation health system stakeholders may wish to consider the following potential barriers to their application

lack of human resources with the necessary expertise and skills to implement supervise and support recommended practices

lack of understanding of changes in recommended interventions among skilled care personnel and systems managers

resistance of skilled care personnel to changing from the use of non-evidence-based to evidence-based practices

lack of infrastructure to support interventions (such as electricity and refrigeration for temperature-sensitive uterotonics)

lack of essential equipment supplies and medicines (such as needles syringes gloves and uterotonics)

lack of effective mechanisms to identify women who are experiencing PPH in order to trigger PPH management pathways and

lack of health information management systems designed to document and monitor recommended practices (such as patient records and registers)

Various strategies for addressing these barriers and facilitating implementation are provided under implementation considerations in section 4

62 Monitoring and evaluating guideline implementationThe implementation and impact of this recommendation will be monitored at the health service country and regional levels as part of broader efforts to monitor and improve the quality of maternal and newborn care The WHO document Standards for improving quality of maternal and newborn care in health facilities (32) provides a list of prioritized input output and outcome measures that can be used to define quality-of-care criteria and indicators and that should be aligned with locally agreed targets In collaboration with the monitoring and evaluation teams of the WHO Department of Sexual and Reproductive Health and Research and the WHO Department of Maternal Newborn Child and Adolescent Health and Ageing data on country- and regional-level implementation of the recommendation will be collected and evaluated in the short to medium term to assess its impact on national policies of individual WHO Member States Interrupted time series clinical audits or criterion-based audits could be used to obtain the relevant data on the use of interventions contained in this guideline

With regard to PPH prevention WHO recommends that the coverage of prophylactic uterotonics be used as a process indicator for the monitoring and prevention of PPH (19) The suggested ldquoprophylactic uterotonic coverage indicatorrdquo is calculated as the number of women receiving prophylactic uterotonics during the third stage of labour divided by all women giving birth This indicator provides an overall assessment of adherence to the recommendation included in this guideline

The use of other locally agreed and more specific indicators (for example the proportion of pregnant women with IV access already in place given IV oxytocin after vaginal birth) may be necessary to obtain a more complete assessment of the quality of care related to the prevention and treatment of PPH WHO has developed specific guidance for evaluating the quality of care for severe maternal complications (including PPH) based on the near miss and criterion-based clinical audit concepts (33) Monitoring of the quality of uterotonic drugs available in low-resource settings may help to guide skilled health personnel in selecting the most effective uterotonic option for PPH prevention in the context in which they are working

7 Updating the recommendation

The Executive GSG convenes annually to review WHOrsquos current portfolio of maternal and perinatal health recommendations and to help WHO prioritize new and existing questions for recommendation development and updating Accordingly this recommendation will be reviewed along with other recommendations and prioritized as needed by the Executive GSG If new evidence that could potentially impact the current evidence base is identified the recommendation may be updated If no new reports or information is identified the recommendation may be revalidated

Following publication and dissemination of the updated recommendation any concerns about the validity of the recommendation should be promptly communicated to the guideline implementers in addition to any plans to update the recommendation

WHO welcomes suggestions regarding additional questions for inclusion in the updated recommendation Please email your suggestions to srhmphwhoint

8 References

1 Trends in maternal mortality 2000 to 2017 estimates by WHO UNICEF UNFPA World Bank Group and the United Nations Population Division executive summary Geneva World Health Organization 2019 (httpsappswhointirishandle10665327596 accessed 9 July 2020)

2 Say L Chou D Gemmill A Tuncalp O Moller AB Daniels J et al Global causes of maternal death a WHO systematic analysis Lancet Glob Health 20142(6)e323ndash33 doi101016S2214-109X(14)70227-X

3 The Sustainable Development Goals report New York (NY) United Nations 2019 (httpsunstatsunorgsdgsreport2019 accessed 9 July 2020)

4 Office of the United Nations High Commissioner for Human Rights Technical guidance on the application of a human rights-based approach to the implementation of policies and programmes to reduce preventable maternal morbidity and mortality Human Rights Council twentieth session New York (NY) United Nations General Assembly 2012 (httpswwwwhointgender-equity-rightsknowledgereduce-maternal-mortalityen accessed 9 July 2020)

5 Tuncalp Ouml Were WM MacLennan C Oladapo OT Gulmezoglu AM Bahl R et al Quality of care for pregnant women and newborns ndash the WHO vision BJOG 2015122(8)1045ndash9 doi1011111471-052813451

6 WHO UNFPA UNICEF ICM ICN FIGO IPA Definition of skilled health personnel providing care during childbirth the 2018 joint statement by WHO UNFPA UNICEF ICM ICN FIGO and IPA Geneva World Health Organization 2018 (httpswwwwhointreproductivehealthpublicationsstatement-competent-mnh-professionalsen accessed 9 July 2020)

7 Carroli G Cuesta C Abalos E Gulmezoglu AM Epidemiology of postpartum haemorrhage a systematic review Best Pract Res Clin Obstet Gynaecol 200822(6)999ndash1012 doi101016jbpobgyn200808004

8 WHO recommendations Uterotonics for the prevention of postpartum haemorrhage World Health Organization 2018 (httpsappswhointirishandle10665277276 accessed 14 July 2020)

9 Souza JP Gulmezoglu AM Vogel J Carroli G Lumbiganon P Qureshi Z et al Moving beyond essential interventions for reduction of maternal mortality (the WHO Multicountry Survey on Maternal and Newborn Health) a cross-sectional study Lancet 2013381(9879)1747ndash55 doi101016S0140-6736(13)60686-8

10 Oyelese Y Ananth CV Postpartum hemorrhage epidemiology risk factors and causes Clin Obstet Gynecol 201053(1)147ndash56 doi101097GRF0b013e3181cc406d

11 Daru J Zamora J Fernandez-Felix BM Vogel J Oladapo OT Morisaki N et al Risk of maternal mortality in women with severe anaemia during pregnancy and post partum a multilevel analysis Lancet Glob Health 20186(5)e548ndash54 doi101016S2214-109X(18)30078-0

12 World Health Organization model list of essential medicines ndash 21st list Geneva World Health Organization 2019 (httpswwwwhointmedicinespublicationsessentialmedicinesen accessed 14 July 2020)

13 Wishart DS Feunang YD Guo AC Lo EJ Marcu A Grant JR et al DrugBank 50 a major update to the DrugBank database for 2018 Nucleic Acids Res 201846(D1)D1074ndash82 doi101093nargkx1037

14 Kim S Thiessen PA Bolton EE Chen J Fu G Gindulyte A et al PubChem substance and compound databases Nucleic Acids Res 201644(D1)D1202ndash13 doi101093nargkv951

15 Vlassoff M Diallo A Philbin J Kost K Bankole A Cost-effectiveness of two interventions for the prevention of postpartum hemorrhage in Senegal Int J Gynaecol Obstet 2016133(3)307ndash11 doi 101016jijgo201510015

16 Vogel JP Dowswell T Lewin S Bonet M Hampson L Kellie F et al Developing and applying a lsquoliving guidelinesrsquo approach to WHO recommendations on maternal and perinatal health BMJ Glob Health 20194(4)e001683 doi101136bmjgh-2019-001683

17 Executive Guideline Steering Group for updating WHO maternal and perinatal health recommendations Geneva World Health Organization 2019 (httpswwwwhointreproductivehealthpublicationsupdating-mnh-recommendationsen accessed 9 July 2020)

18 WHO handbook for guideline development second edition Geneva World Health Organization 2014 (httpsappswhointirishandle10665145714 accessed 9 July 2020)

19 WHO recommendations for the prevention and treatment of postpartum haemorrhage Geneva World Health Organization 2012 (httpswwwwhointreproductivehealthpublicationsmaternal_perinatal_health9789241548502en accessed 9 July 2020)

20 Downe S Finlayson K Oladapo OT Bonet M Gulmezoglu AM What matters to women during childbirth a systematic qualitative review PloS One 201813(4)e0194906 doi101371journalpone0194906

21 Finlayson K Downe S Vogel JP Oladapo OT What matters to women and healthcare providers in relation to interventions for the prevention of postpartum haemorrhage a qualitative systematic review PloS One 201914(5)e0215919 doi101371journalpone0215919

22 Lawrie TA Rogozinska E Sobiesuo P Vogel JP Ternent L Oladapo OT A systematic review of the cost-effectiveness of uterotonic agents for the prevention of postpartum hemorrhage Int J Gynaecol Obstet 2019146(1)56ndash64 doi101002ijgo12836

23 Meher S Cuthbert A Kirkham JJ Williamson P Abalos E Aflaifel N et al Core outcome sets for prevention and treatment of postpartum haemorrhage an international Delphi consensus study BJOG 2019126(1)83ndash93 doi1011111471-052815335

24 Oladapo OT Okusanya BO Abalos E Intramuscular versus intravenous prophylactic oxytocin for the third stage of labour Cochrane Database Syst Rev 20189CD009332 doi10100214651858CD009332pub3

25 GRADEpro GDT GRADEpro Guideline Development Tool [Software] McMaster University (developed by Evidence Prime Inc) 2015 (httpswwwgradeproorg accessed 14 July 2020)

26 Alonso-Coello P Schunemann HJ Moberg J Brignardello-Petersen R Akl EA Davoli M et al GRADE Evidence to Decision (EtD) frameworks a systematic and transparent approach to making well informed healthcare choices 1 Introduction BMJ 2016353i2016 doi101136bmji2016

27 Lewin S Booth A Glenton C Munthe-Kaas H Rashidian A Wainwright M et al Applying GRADE-CERQual to qualitative evidence synthesis findings introduction to the series Implement Sci 201813(Suppl 1)2 doi101186s13012-017-0688-3

28 Adnan N Conlan-Trant R McCormick C Boland F Murphy DJ Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery randomised controlled trial BMJ 2018362k3546 doi101136bmjk3546

29 Neri-Mejia M Pedraza-Aviles AG [Active management of the third stage of labor Three schemes of oxytocin randomised clinical trial] Ginecol Obstet Mex 201684(5)306ndash13

30 Thomas JS Koh SH Cooper GM Haemodynamic effects of oxytocin given as iv bolus or infusion on women undergoing Caesarean section Br J Anaesth 200798(1)116ndash9 doi101093bjaael302

31 Pinder AJ Dresner M Calow C Shorten GD OrsquoRiordan J Johnson R Haemodynamic changes caused by oxytocin during caesarean section under spinal anaesthesia Int J Obstet Anesth 200211(3)156ndash9 doi101054ijoa20020970

32 Standards for improving quality of maternal and newborn care in health facilities Geneva World Health Organization 2016 (httpswwwwhointmaternal_child_adolescentdocumentsimproving-maternal-newborn-care-qualityen accessed 14 July 2020)

33 Evaluating the quality of care for severe pregnancy complications the WHO near-miss approach for maternal health Geneva World Health Organization 2011 (httpsappswhointirishandle1066544692 accessed 14 July 2020)

Annex 1 External experts and WHO staff involved in the preparation of the recommendation

Participants at the WHO Guideline Development Group (GDG) Meeting (11ndash12 March 2020)

GUIDELINE DEVELOPMENT GROUP (GDG)

Oluwarotimi Ireti AKINOLAPresidentSociety of Gynaecology and Obstetrics in Nigeria (SOGON)Abuja Nigeria

Melania AMORIM Obstetrician amp Gynaecologist Instituto Paraibano de Pesquisa Professor Joaquim Amorim Neto and Instituto de Medicina Integral Professor Fernando FigueiraParaiba Brazil

Brendan CARVALHO Chief Division of Obstetric AnaesthesiaDepartment of Anaesthesiology Perioperative and Pain MedicineStanford University School of MedicineStanford United States of America (USA)

Catherine DENEUX-THARAUX Obstetrical Perinatal and Pediatric Epidemiology Research Team Centre of Research in Epidemiology and Statistics Sorbonne Paris France

Tippawan LIABSUETRAKUL Professor of Epidemiology Faculty of Medicine Prince of Songkhla UniversitySongkhla Thailand

Martin MEREMIKWU Professor of Paediatrics amp Clinical Epidemiology University of CalabarCalabar Nigeria

Suellen MILLER Director Safe Motherhood ProgramDepartment of Obstetrics Gynecology and Reproductive SciencesUniversity of California San FranciscoSan Francisco USA

Ashraf NABHANProfessorDepartment of Obstetrics and GynecologyAin Shams UniversityCairo Egypt

Mari NAGAIDeputy Director Health System Team LeadBureau of International Health CooperationNational Center for Global Health and Medicine Tokyo Japan

Hayfaa WAHABI Professor and ChairEvidence-based Healthcare and Knowledge TranslationCollege of Medicine King Saud UniversityRiyadh Saudi Arabia

Dilys WALKER ProfessorDepartment of Obstetrics Gynecology amp Reproductive SciencesUCSFSan Francisco USA

Andrew WEEKSProfessorUniversity of LiverpoolLiverpool United Kingdom of Great Britain and Northern Ireland (United Kingdom)

Participated by video conference

OBSERVERS

Deborah ARMBRUSTER Senior Maternal and Newborn Health AdvisorUnited States Agency for International Development (USAID) Bureau for Global HealthJakarta Indonesia

Carlos FUCHTNER President International Federation of Gynaecology and Obstetrics (FIGO) Santa Cruz Bolivia

Ingela WIKLUND RepresentativeInternational Confederation of Midwives (ICM) Stockholm Sweden

EVIDENCE SYNTHESIS GROUP (ESG)

Edgardo ABALOS Vice DirectorCentro Rosarino de Estudios Perinatales Rosario Argentina

Virginia DIAZ Centro Rosarino de Estudios Perinatales Rosario Argentina

Kenneth FINLAYSON (Methodologist)Research AssociateResearch in Childbirth and Health Unit (ReaCH)University of Central LancashirePreston United Kingdom

Leanne JONES (Methodologist)Research AssociateCochrane Pregnancy and Childbirth Group Editorial OfficeUniversity of LiverpoolLiverpool United Kingdom

Frances KELLIE Managing EditorCochrane Pregnancy and Childbirth Group Editorial OfficeUniversity of LiverpoolLiverpool United Kingdom

Myfanwy WILLIAMS (Methodologist)Research AssociateCochrane Pregnancy and Childbirth Group Editorial OfficeUniversity of LiverpoolLiverpool United Kingdom

Participated by video conference Unable to attend

EXTERNAL REVIEW GROUP (ERG)

Christine EASTProfessor of Nursing and Midwifery NursingLa Trobe UniversityMelbourne Australia

Gill GYTEConsumer Editor for Cochrane Pregnancy amp Childbirth GroupUniversity of LiverpoolLiverpool Womenrsquos Hospital NHS Trust Crown StreetLiverpool United Kingdom

Justus HOFMEYRDirector Effective Care Research UnitUniversity of the WitwatersrandUniversity of Fort Hare Eastern Cape Department of HealthEastern Cape South Africa

Syeda Batool MAZHARProfessor of Obstetrics and GynaecologyMother and Child Health Centre (MCH) Pakistan Institute of Medical SciencesIslamabad Pakistan

Enrique OYARZUNChairman Department Obstetrics and GynaecologyFacultad de Medicina PontificiaUniversidad Catoacutelica de ChileSantiago Chile

Qian XUDepartment of Maternal Child and Adolescent HealthSchool of Public Health Fudan UniversityShanghai China

WHO COUNTRY AND REGIONAL OFFICERS

Nino BERDZULISexual and Reproductive Health Noncommunicable Diseases and life-course WHO Regional Office for Europe Copenhagen Denmark

Bremen DE MUCIOSexual and Reproductive Health WHO Regional Office of the Americas Montevideo Uruguay

Hayfa ELAMIN Regional Adviser Reproductive Maternal Health and AgeingWHO Regional Office for the African RegionHarare Zimbabwe

Chandani Anoma JAYATHILAKAFamily Health Gender and Life Course WHO Regional Office for South-East Asia New Delhi India

Ramez Khairi MAHAINIReproductive and Maternal HealthWHO Regional Office for the Eastern Mediterranean Cairo Egypt

Howard SOBELReproductive Maternal Newborn Child and Adolescent Health Division of NCD and Health through Life-CourseRegional Office for the Western Pacific Manila Philippines

Claudio SOSARegional Advisor AMROCLPSexual and Reproductive HealthWHO Regional Office for the AmericasMontevideo Uruguay

Unable to attend

WHO STEERING GROUPdepartment of sexual and reproductive health and research

Fernando ALTHABEMedical OfficerMaternal and Perinatal HealthSexual and Reproductive Health and Research

Tina LAVINTechnical OfficerMaternal and Perinatal HealthSexual and Reproductive Health and Research

Olufemi T OLADAPO Unit Head aiMaternal and Perinatal HealthSexual and Reproductive Health and Research

Joshua P VOGELConsultantMaternal and Perinatal HealthSexual and Reproductive Health and Research

Mariana WIDMERTechnical OfficerMaternal and Perinatal HealthSexual and Reproductive Health and Research

department of maternal newborn Child Adolescent health and Ageing

Maurice BUCAGOMedical OfficerMaternal Health Unit Maternal Newborn Child and Adolescent Health and Ageing

Annex 2 Priority outcomes used in decision-making

Critical outcomes Maternal death

PPH ge 1000 mL

Blood transfusion

Important outcomes Severe maternal morbidity intensive care unit admission

Severe maternal morbidity shock

Postpartum haemorrhage ge 500 mL

Use of additional uterotonics

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

Maternal satisfaction

1 This includes any side-effect of the intervention or side-effect requiring treatment including nausea vomiting headache abdominal pain hypotension shivering fever and diarrhoea

Annex 3 Summary and management of declared interests from GDG members

name expertise contributed to guideline development declared interest management of conflict of

interest

Oluwarotimi I Akinola

Content expert and end-user

None declared Not applicable

Melania Amorim Content expert and end-user

Brendan Carvalho Content expert and end-user

Serves as technical consultant for Gauss Surgical (company that measures peripartum and operative blood loss)

Receives share options from Gauss Surgical

The conflict was not considered serious enough to affect Guideline Development Group (GDG) membership or participation

Catherine Deneux-Tharaux

Tippawan Liabsuetrakul

Martin Meremikwu Content expert and end-user

Suellen Miller Content expert and end-user

Serves as a technical advisor to the Blue Fuzion Group who manufactures and distributes one brand of non-pneumatic anti-shock garment the LifeWrap UCSF receives a royalty for the trademark

The conflict was not considered serious enough to affect GDG membership or participation

Ashraf Nabhan Content expert and implementer

Mari Nagai Content expert and end-user

Hayfaa Wahabi Content expert and end-user

Dilys Walker Content expert and end-user

Co-founder and President of the nongovernmental organization PRONTO International PRONTO designs and implements simulation and team training for obstetric and neonatal emergencies including postpartum haemorrhage Professor Walker has donated funds to the organization PRONTO International has the rights to the low-tech birth simulator PARTO Pants and the PRONTO Pack simulation training kit

interest

Andrew Weeks Content expert and end-user

Chief investigator of the COPE trial and co-inventor of the Butterfly device to treat postpartum haemorrhage as well as chief investigator of the development study Both funded by NIHR (United Kingdom) research grants to the University of Liverpool The University is the device patent holder but as co-inventor Professor Weeks would receive a share of the profits

Annex 4 Evidence to Decision framework

QuestionFollowing is the question of interest in PICO (population (P) intervention (I) comparator (C) outcome (O)) format

For women in the third stage of labour (P) does administration of IV oxytocin for postpartum haemorrhage (PPH) prevention (I) compared with IM oxytocin (C) improve maternal and infant outcomes (O)

Problem Preventing the onset of PPH

Perspective Clinical practice recommendation ndash population perspective

Population (P) Women in the third stage of labour with vaginal birth

Intervention (I) IV oxytocin

Comparator (C) IM oxytocin

Setting Hospital or community setting

Subgroups By type of IV administration by type of further management

Priority outcomes (O)1

PPH ge 1000 mL

Blood transfusion

Important outcomes Severe maternal morbidity intensive care unit (ICU) admission

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

1 These outcomes reflect the prioritized outcomes used in the development of this recommendation in WHO recommendations for the prevention and treatment of postpartum haemorrhage (2012) The outcomes ldquomaternal well-beingrdquo and ldquomaternal satisfactionrdquo have been added as part of this update

2 This includes any side-effect of the intervention or side-effect requiring treatment including nausea vomiting headache abdominal pain hypotension shivering fever and diarrhoea A

AssessmentEffects of interventionsWhat is the effect of IV oxytocin versus IM oxytocin for PPH prevention on the priority outcomes

Research evidence

Summary of evidenceSource and characteristics of studiesEvidence on the effects of IV versus IM oxytocin for the prevention of PPH following vaginal birth was derived from an update of a Cochrane systematic review which included seven randomized trials (7840 women) (4) Data were extracted from all seven trials (data for 7777 women were analysed 40 women from one trial were not included because they gave birth by caesarean section after recruitment and 23 from another trial were excluded because they were given an oxytocin IV infusion after the third stage of labour) Trials were conducted in hospital settings in Argentina Egypt Ireland Mexico Thailand and Turkey (two trials) between 2010 and 2019 All trials were single-centre except for Egypt (two hospitals)

The number of women included in the trials ranged from 66 to 4913 the largest trial contributed 63 of the total sample All trials included women with singleton pregnancies only four trials included women at term and the other three included women at all gestational ages (although most women were at term) All trials recruited women in labour two trials randomized either when women were in active labour or when delivery was imminent three randomized when women were admitted to an assessment unit or labour ward while in labour and two were not specific as to when randomization occurred though the available information suggests it was when the women were in active labour

Two trials (1555 women) administered a placebo to all women while four trials did not mask women or clinicians to the treatment allocation and in the remaining trial this was not clear The third stage of labour was managed actively in four of the included studies (all of these trials used controlled cord traction two trials delayed cord clamping and two trials also mention the use of uterine massage) In two studies active management was not implemented and in the final study this was again unclear

Of the seven trials four were two-arm trials two were three-arm trials and one was a four-arm trial The three-arm trials both compared IM oxytocin with an IV bolus and an IV infusion In one of these trials the IV arms were combined into a single pair-wise comparison In the other three-arm trial only two arms were eligible for inclusion because one did not take place in the third stage of labour The four-arm trial compared IM and IV bolus at the birth of the anterior shoulder and at clamping of the cord The review combined the IM groups and IV groups at each time point to make a single pair-wise comparison

All seven trials used 10 IU of IM oxytocin either with the birth of the anterior shoulder or immediately following the birth All trials used 10 IU of IV oxytocin given within the same time frame as IM oxytocin The rates of administration of IV oxytocin differed across trials over 1 minute (three trials) in 1000 mL saline at a rate of 1 mLmin (one trial) in 500 mL saline solution at a rate of 12 mLmin (one trial) in 10 mL of saline solution slowly administered over 2 minutes (one trial) The largest trial had three arms ndash the Cochrane review pooled the two IV arms for meta-analysis combining women receiving IV oxytocin 10 IU in 500 mL saline through a gravity-driven infusion with the roller clamp fully open with women receiving IV oxytocin 10 IU over 1 minute

Effects of IV oxytocin compared with IM oxytocinMaternal death It is unclear whether the route of administration of oxytocin has an impact on the risk of this outcome as there were no maternal deaths in either group (very low certainty)

PPH ge 1000 mL Moderate-certainty evidence suggests that the risk of this outcome is probably decreased with IV oxytocin when compared with IM oxytocin (four trials 6681 women 473692 versus 692989 average risk ratio [RR] 065 95 confidence interval [CI] 039 to 108) However the 95 CI crosses the line of no effect

Blood transfusion High-certainty evidence suggests that women are less likely to need a blood transfusion if they receive IV oxytocin when compared with IM oxytocin (four trials 6684 women 193693 versus 402991 average RR 044 95 CI 026 to 077)

Severe maternal morbidity ndash ICU admission The Cochrane review reported a combined outcome of serious maternal morbidity however 94 of the pooled effect estimate came from one trial reporting high-dependency unit admissions Moderate-certainty evidence suggests that IV oxytocin probably decreases the risk of this outcome when compared with IM oxytocin (four trials 7028 women 93 865 versus 203163 average RR 047 95 CI 022 to 100) However the 95 CI touches the line of no effect

PPH ge 500 mL High-certainty evidence suggests that the risk of blood loss ge 500 mL decreases when women receive IV oxytocin compared with IM oxytocin (six trials 7731 women 2014 217 versus 2533514 average RR 078 95 CI 066 to 092)

Use of additional uterotonics Low-certainty evidence suggests that the need for additional uterotonics may decrease with IV oxytocin when compared with IM oxytocin (six trials 7327 women 1794014 versus 2073313 average RR 078 95 CI 049 to 125) However the 95 CI crosses the line of no effect

Blood loss Six trials (7541 women) in the Cochrane review reported on mean blood loss The review authors did not pool the data to perform a meta-analysis because the standard deviations (SDs) in the six studies varied considerably The individual studies suggest that mean blood loss may decrease with IV oxytocin compared with IM oxytocin However the review authors observed that the mean blood loss was low across studies and the difference between the groups is unlikely to be clinically important The studies contributing data to this outcome varied in their risk of bias and only two of six trials were at low risk of bias

Postpartum anaemia High-certainty evidence suggests that there is little or no difference in the incidence of postpartum anaemia in women who have received IV or IM oxytocin (three trials 6178 women 2273444 versus 2222744 average RR 099 95 CI 084 to 116)

Breastfeeding High-certainty evidence suggests that the route of administration of oxytocin in the third stage of labour makes little or no difference to whether women are not breastfeeding at hospital discharge (one trial 1035 women 228517 versus 238518 average RR 096 95 CI 084 to 110)

Side-effects Moderate-certainty evidence suggests that IV oxytocin probably decreases the risk of any adverse effect reported when compared with IM administration (one trial 1035 women 21517 versus 27518 average RR 078 95 CI 045 to 136) However the 95 CI crosses the line of no effect

In terms of specific side-effects moderate-certainty evidence suggests that the route of oxytocin administration probably makes little or no difference to hypotension (four trials 6468 women 3893585 versus 3212883 average RR 101 95 CI 088 to 115) and tachycardia (two trials 1513 women 75756 versus 85757 average RR 089

95 CI 068 to 116) Low-certainty evidence suggests that the route may make little or no difference to nausea (two trials 1515 women 1756 versus 1759 average RR 100 95 CI 006 to 1598) while IV oxytocin may make little or no difference to the risk of headache (two trials 1515 women 3756 versus 4759 average RR 075 95 CI 017 to 334) and shivering (two trials 1515 women 2756 versus 5759 average RR 040 95 CI 008 to 206) It is unclear what effect the route of oxytocin administration has on diarrhoea (one trial 480 women low certainty) fever (gt 38 degC reported) (one trial 480 women low certainty) and vomiting (two trials 1515 women low certainty) because there were no events in the trials reporting on these outcomes while sample sizes were relatively small

Maternal satisfaction No included trials reported this outcome

The priority outcomes shock abdominal pain hypertension and maternal well-being were not reported in the Cochrane review

Subgroup analyses by type of IV administrationThe review analysed the results for two outcomes (PPH ge 1000 mL and serious maternal morbidity) by type of IV administration (bolus or infusion) There was no evidence of a difference between the subgroups for severe blood loss The subgroup effects were unclear for serious maternal morbidity because there were no events in the trials administering oxytocin by IV infusion

Subgroup analyses by type of managementThe review also analysed results for PPH ge 1000 mL and serious maternal morbidity by type of further management (with or without active management of the third stage of labour) However the subgroups were too imbalanced in size to support a meaningful comparison of subgroups by type of further management

Additional considerations

The Cochrane review authors conducted a sensitivity analysis restricted to trials at low risk of selection bias for the outcomes PPH ge 1000 mL and serious maternal morbidity Results from trials at low risk of bias suggest that administration of IV oxytocin decreases the risk of PPH ge 1000 mL compared with IM oxytocin (two trials 1512 women 38755 versus 60757 average RR 064 95 CI 043 to 094)

However while the point estimate for serious maternal morbidity suggests a probable decrease in risk with IV oxytocin the 95 CI crosses the line of no effect (two trials 1515 women 9756 versus 19759 RR 047 95 CI 022 to 104)

Desirable effectsHow substantial are the desirable anticipated effects of IV oxytocin versus IM oxytocin

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Undesirable effectsHow substantial are the undesirable anticipated effects of IV oxytocin versus IM oxytocin

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

Certainty of the evidenceWhat is the overall certainty of the evidence on effects of IV oxytocin versus IM oxytocin

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

ValuesIs there important uncertainty about or variability in how much women (and their families) value the main outcomes associated with the route of oxytocin for PPH prevention

Research evidence

In a review of qualitative studies evaluating ldquowhat women wantrdquo from intrapartum care findings indicate that most women want a normal birth (with good outcomes for mother and baby) but acknowledge that medical intervention may sometimes be necessary (high confidence) (5) Most women especially those giving birth for the first time are apprehensive about labour and birth (high confidence) and wary of medical interventions although in certain contexts andor situations women welcome interventions to address recognized complications (low confidence) Where interventions are introduced women would like to receive relevant information from technically competent health-care providers who are sensitive to their needs (high confidence)

Findings from another qualitative systematic review exploring perceptions of PPH prevention and treatment among women and providers suggest that women do not recognize the clinical definitions of blood loss or what might be considered ldquonormalrdquo blood loss (moderate confidence) (6) Furthermore in some low- and middle-income countries (LMICs) women place a greater value on the expulsion of so-called ldquodirty bloodrdquo which they perceive as a normal cleansing process and something that should not be prevented (moderate confidence)

The same review highlighted womenrsquos need for information about PPH ideally given during antenatal care (moderate confidence) and the importance of kind clinically competent staff with a willingness to engage in shared decision-making around PPH management (moderatelow confidence) In addition it was found that women are concerned about feelings of exhaustion and anxiety (at being separated from their babies) following PPH as well as the long-term psychological effects of experiencing PPH and the negative impact this may have on their ability to breastfeed (moderatelow confidence)

Judgement

mdashImportant uncertainty

or variability

mdashPossibly important

uncertainty or variability

Probably no important uncertainty or

variability

mdashNo important uncertainty or

variability

Balance of effectsDoes the balance between desirable and undesirable effects favour IV oxytocin or IM oxytocin

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

ResourcesHow large are the resource requirements (costs) of IV oxytocin for PPH prevention

Research evidence

A systematic review of the literature updated until 2020 found no direct evidence on the costs and cost-effectiveness of IM oxytocin compared with IV oxytocin to prevent PPH (7)

Both IV and IM oxytocin require administration by skilled health personnel However the administration of IV oxytocin requires intravenous access which may slightly increase cost due to the need for IV equipment (such as cannulae and IV fluids)

Considering the differences between IV and IM oxytocin in their effectiveness on priority outcomes that are associated with management costs (such as blood transfusion ICU admission and adverse effects) it is possible that IV oxytocin would be more cost-effective However the Guideline Development Group (GDG) noted that the cost-effectiveness would likely differ between higher- and lower-resource settings

Both IV and IM oxytocin require refrigerated storage and transport which are not readily available in many low-resource settings (8) Concerns about the quality of oxytocin supplies and wastage due to heat compromise and expiry have been reported (9)

main resource requirements

resource description

Staff Oxytocin requires parenteral administration (IV or IM) by skilled health-care personnel

Training Training to administer injections and to monitor and manage expected and unexpected side-effects is part of standard maternity staff training However some additional training may be required if a route of administration of oxytocin is introduced in settings where it has not previously been available

Supplies Oxytocin indicative costCost per 10 IU US$ 022ndash119 (1011)IM administration Needle and syringeIV administration

IV-givinginfusion set with needle Sterile disposable IV cannula IV fluids

Equipment and infrastructure

Cold chain storage and transport costs Cost per birth is possibly US$ 084 in a low-resource setting (12)

Time IM administration takes 2 minutesIV administration takes longer if an IV cannula needs to be put in place for this purpose (13)

Supervision and monitoring

Supervision and monitoring to ensure appropriate use stock availability and quality

Resources requiredJudgement

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashNegligible costs or savings

mdashModerate

savings

mdashLarge

savings

Certainty of the evidence on required resourcesWhat is the certainty of the evidence on costs

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectivenessJudgement

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashFavours IV oxytocin

EquityWhat would be the impact of IV oxytocin for PPH prevention on health equity

Research evidence

No direct evidence identified

Oxytocin in injectable form (whether IV or IM) is relatively inexpensive and is already widely available in a range of resource settings (low to high) However according to the findings from a qualitative systematic review looking at the prevention and treatment of PPH inconsistent stock levels and the heat sensitivity of the medication may limit its use in low-resource settings in LMICs particularly in isolated rural areas where the need is arguably greatest (moderate confidence) (6) In some contexts (for example India and Sierra Leone) supply issues have resulted in women and health-care professionals turning to private suppliers to purchase oxytocin at additional cost to themselves in order to fulfil guideline recommendations These challenges are likely to affect both IV oxytocin and IM oxytocin

The 2015 World Health Organization (WHO) State of inequality report indicates that women who are poor least educated and who reside in rural areas have lower coverage of health interventions and worse health outcomes than more advantaged women (14) IV oxytocin may decrease equity as it can be more difficult for women to access it (due to the need for IV access)

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashProbably increased

mdashIncreased

AcceptabilityIs IV oxytocin for PPH prevention acceptable to key stakeholders

Research evidence

No direct evidence relating to the acceptability of (or preference for) a particular administration route for oxytocin from either women or health-care providers was identified

IV oxytocin is widely used internationally and in a range of resource settings (low to high)

Indirect findings from a qualitative systematic review exploring perceptions of PPH prevention and treatment by women and health-care providers indicate that providers recognize the benefits of using oxytocin (usually via a single IV injection) to prevent PPH and hasten the delivery of the placenta (moderate confidence) (6) However in some LMIC settings providers hold the perception that the medication may cause retained placenta when administered preventatively or may even contribute to PPH when given to induce labour (moderate confidence) In rural LMIC settings where access to health facilities may be limited community-based health providers (usually traditional birth attendants) prefer to use herbal medicines with uterotonic properties (moderate confidence) while in several high-income countries experienced midwives use expectant management and make selective use of guideline recommendations

(ignoring oxytocin use) especially if the birth is perceived to be normal (moderate confidence) There were no findings from studies of womenrsquos perceptions relating to the acceptability of oxytocin

The GDG noted the lack of direct evidence on acceptability However they noted the aforementioned evidence that women prefer a normal birth and considered that in some situations the presence of an IV line andor the administration of IV fluids around the time of childbirth may cause some discomfort or restrict a womanrsquos mobility However in situations where a woman already has IV access in place (for other medical reasons) it is likely that women would find IV oxytocin administration to be acceptable

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

FeasibilityIs IV oxytocin for PPH prevention feasible to implement

Research evidence

No direct evidence relating to the feasibility of a particular administration route for oxytocin from either women or health-care providers was identified However IV oxytocin is widely used internationally and in a range of resource settings (low to high)

Indirect findings from a qualitative systematic review exploring perceptions of PPH prevention and treatment among women and health-care providers suggest that resource constraints may influence effective use of oxytocin for PPH prevention particularly in LMICs (high confidence) (6) Inconsistent supplies and concerns about oxytocin storage in areas with limitedinconsistent electricity hinder utilization and a lack of experienced staff to administer the injection limits its use in certain contexts (high confidence) In a wide variety of settings health-care providers feel they need more training in PPH management as well as specific training on whenhow to administer oxytocin (high confidence) In some LMIC settings task shifting had been introduced to address staff shortages or increase coverage and the success of this strategy was largely dependent on the ability of health-care professionals to build trustworthy relationships with traditional birth attendants or community health workers (moderate confidence) (6) There were no findings from the reviewed studies on womenrsquos perceptions relating to the feasibility of this particular intervention

Injectable oxytocin is already widely available in a range of resource settings (low to high) and has multiple applications (such as PPH prevention and treatment as well as labour induction) Oxytocin (10 IU in 1 mL for injection) is listed in the WHO model list of essential medicines (3)

The GDG noted however that lack of access to equipment and fluids for IV administration as well as the need to have staff that can safely manage IV infusions may limit feasibility of IV oxytocin particularly in lower-level facilities in limited-resource settings

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Summary of judgements tableDesirable effects

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

Certainty of the evidence

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

Values mdashImportant

mdashPossibly

important uncertainty or

variability

Probably no important

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

Certainty of the evidence on required resources

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Equity mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Acceptability Donrsquot know

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Feasibility mdashDonrsquot know

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Annex 4 evidence to decision frAmework

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

who reCommendAtion on routes of oxytoCin AdministrAtion for the prevention of postpArtum hAemorrhAge After vAginAl birth

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

References1 Wishart DS Feunang YD Guo AC Lo EJ Marcu A Grant JR et al DrugBank

50 a major update to the DrugBank database for 2018 Nucleic Acids Res 201846(D1)D1074ndash82 doi101093nargkx1037

2 Kim S Thiessen PA Bolton EE Chen J Fu G Gindulyte A et al PubChem Substance and Compound databases Nucleic Acids Res 201644(D1)D1202ndash13 doi101093nargkv951

5 Downe S Finlayson K Oladapo OT Bonet M Gulmezoglu AM What matters to women during childbirth A systematic qualitative review PloS One 201813(4)e0194906 doi101371journalpone0194906

6 Finlayson K Downe S Vogel JP Oladapo OT What matters to women and healthcare providers in relation to interventions for the prevention of postpartum haemorrhage A qualitative systematic review PloS One 201914(5)e0215919 doi101371journalpone0215919

8 Natarajan A Ahn R Nelson BD Eckardt M Kamara J Kargbo S et al Use of prophylactic uterotonics during the third stage of labor a survey of provider practices in community health facilities in Sierra Leone BMC pregnancy and childbirth 201616(1)23 doi101186s12884-016-0809-z

9 Braddick L Tuckey V Abbas Z Lissauer D Ismail K Manaseki-Holland S et al A mixed-methods study of barriers and facilitators to the implementation of postpartum hemorrhage guidelines in Uganda Int J Gynaecol Obstet 2016132(1)89ndash93 doi101016jijgo201506047

10 Lang DL Zhao FL Robertson J Prevention of postpartum haemorrhage cost consequences analysis of misoprostol in low-resource settings BMC Pregnancy Childbirth 201515(1)305 doi101186s12884-015-0749-z

11 Gallos ID Papadopoulou A Man R Athanasopoulos N Tobias A Price MJ et al Uterotonic drugs for preventing postpartum haemorrhage a network meta-analysis and cost-effectiveness analysis Cochrane Database Syst Rev 201812(12)CD011689 doi10100214651858CD011689pub3

12 Vlassoff M Diallo A Philbin J Kost K Bankole A Cost-effectiveness of two interventions for the prevention of postpartum hemorrhage in Senegal Int J Gynaecol Obstet 2016133(3)307ndash11 doi101016jijgo201510015

13 Avenir Health OneHealth Tool intervention assumptions Avenir Health 2016 (httpswwwavenirhealthorgsoftware-onehealth accessed 14 July 2020)

14 State of inequality reproductive maternal newborn and child health Geneva World Health Organization 2015 (httpswwwwhointghohealth_equityreport_2015 accessed 10 July 2020)

for more information please contact

world health organizationAvenue Appia 20 Ch-1211 geneva 27 switzerland

maternal and perinatal health unit department of sexual and reproductive health and researche-mail srhmphwhointWebsite wwwwhointreproductivehealth

department of maternal newborn Child Adolescent health and Ageing email mncahwhointWebsite wwwwhointmaternal_child_adolescent

_GoBack

WHO recommendation onRoutes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth

Introduction vii

Target audience vii

Recommendation viii

1 Introduction 1

11 Background 1

2 Methods 3

214 Peer review 9

42 Adaptation 12

8 References 16

Acknowledgements

IM intramuscular

IV intravenous

Executive summary

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

Introduction vii

Target audience vii

Recommendation viii

1 Introduction 1

11 Background 1

2 Methods 3

214 Peer review 9

42 Adaptation 12

8 References 16

Acknowledgements

IM intramuscular

IV intravenous

Executive summary

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

Introduction vii

Target audience vii

Recommendation viii

1 Introduction 1

11 Background 1

2 Methods 3

214 Peer review 9

42 Adaptation 12

8 References 16

Acknowledgements

IM intramuscular

IV intravenous

Executive summary

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

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㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

Acknowledgements

IM intramuscular

IV intravenous

Executive summary

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

Acknowledgements

IM intramuscular

IV intravenous

Executive summary

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

IM intramuscular

IV intravenous

Executive summary

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

Executive summary

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

1 Introduction

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

2 Methods

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

8 References

OBSERVERS

Unable to attend

PPH ge 1000 mL

Blood transfusion

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects1

Maternal well-being

interest

PPH ge 1000 mL

Blood transfusion

PPH ge 500 mL

Blood loss (mL)

Postpartum anaemia

Breastfeeding

Side-effects2

Maternal well-being

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderatemdash

Judgement

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderatemdash

Research evidence

Judgement

or variability

variability

Judgement

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Research evidence

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate costs

mdashModerate

savings

mdashLarge

savings

Judgement

No included studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Donrsquot knowmdash

Variesmdash

Favours IM oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Research evidence

Judgement

mdashDonrsquot know

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

Research evidence

Judgement

Donrsquot knowmdash

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Research evidence

Judgement

mdashDonrsquot know

VariesmdashNo

mdashProbably No

mdashProbably Yes

mdashYes

mdashDonrsquot know

mdashVaries

mdashTrivial

mdashSmall

Moderate

mdashLarge

Undesirable effects

mdashDonrsquot know

mdashVaries

mdashLarge

mdashModerate

mdashSmall

Trivial

mdashNo included

studies

mdashVery low

mdashLow

Moderate

mdashHigh

mdashPossibly

variability

Balance of effects

mdashDonrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

Favours IV oxytocin

Resources required

mdashDonrsquot know

mdashVaries

mdashLarge costs

Moderate

mdashModerate

savings

mdashLarge savings

No included

studies

mdashVery low

mdashLow

mdashModerate

mdashHigh

Cost-effectiveness

Donrsquot know

mdashVaries

mdashFavours IM

oxytocin

mdashProbably

favours IM oxytocin

mdashDoes not

favour either

mdashProbably

favours IV oxytocin

mdashVaries

mdashReduced

Probably reduced

mdashProbably no

impact

mdashIncreased

mdashVaries

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

Varies

mdashNo

mdashProbably No

mdashProbably Yes

mdashYes

㊉㊀

㊀㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

㊉㊀

In ndash

mdashmdash

㊉㊀

㊉㊉

ndash n

ndashndash

ndash ndash

ndashndash

㊉㊉

㊉㊀

㊉㊉

㊉㊀

㊉㊉

ndash n

mdashmdash

n ndash

mdashmdash

mdashIM

) at m

ith IV

sup2=61

_GoBack

Documents

WHO recommendation on Routes of oxytocin administration ......O MMEnDATI O n O n RO UTES O f O XyT O CIn ADMInISTRATI O Recommendation WHO recommendation on routes of oxytocin administration